Recent advances in vaccine delivery system engineering have succeeded in refining the antigen-immune cell interface to substantially improve the adaptive immune response to recombinant subunit vaccine antigens (Azad et al., “Vaccine Delivery—Current Trends and Future,” Curr. Drug Deliv. 3:137-146 (2006); Schijns and Degen, “Vaccine Immunopotentiators of the Future,” Clin. Pharmacol. Ther. 82:750-755 (2007); Huang et al., “Recombinant Immunotherapeutics: Current State and Perspectives Regarding the Feasibility and Market,” Appl. Microbiol. Biotechnol. 87:401-410 (2010); Swartz et al., “Engineering Approaches to Immunotherapy,” Sci. Transl. Med. 4 (2012)). Increasingly, this success has come from innovations in the application of synthetic or biologically-derived nanoparticle antigen carriers (Swartz et al., “Engineering Approaches to Immunotherapy,” Sci. Transl. Med. 4 (2012); Singh et al., “Nanoparticles and Microparticles as Vaccine-Delivery Systems,” Expert Rev. Vaccines 6:797-808 (2007); Metcalfe and Fahmy, “Targeted Nanotherapy for Induction of Therapeutic Immune Responses,” Trends Mol. Med. 18:72-80 (2012)). Nanoparticulate carriers have succeeded in capturing more holistic interactions with pathogens that extend beyond simple antigen identification (Bryan, “Developing an HPV Vaccine to Prevent Cervical Cancer and Genital Warts,” Vaccine 25:3001-3006 (2007)), and allow more efficient and targeted dissemination of antigen to key immune cell populations (Sanders et al., “ISCOM-Based Vaccines: the Second Decade,” Immunol Cell Biol 83:119-129 (2005)). By transitioning the focus of vaccine design to biomolecular and materials engineering, important barriers of adaptive immunity engagement and effective memory response enhancement have been effectively challenged. With this success, however, it has become clear that there remains a marked inability of current subunit vaccine technology to generate protective pathogen-specific TH1-biased cellular immunity (Bevan, “Understand Memory, Design Better Vaccines,” Nat. Immunol. 12:463-465 (2011)) while addressing pathogenic source-related constraints (Huang et al., “Recombinant Immunotherapeutics: Current State and Perspectives Regarding the Feasibility and Market,” Appl. Microbiol. Biotechnol. 87:401-410 (2010); Yoo et al., “Bio-Inspired, Bioengineered and Biomimetic Drug Delivery Carriers,” Nat. Rev. Drug Discov. 10:521-535 (2011)) such as the compatibility challenge of recombinant antigen integration and minimizing the risk of disease transmission. Similarly, challenges pertaining to global health applications of novel, often prohibitively expensive vaccine technology also remain markedly unsolved.
The present invention in directed to overcoming these and other deficiencies in the art.